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  • 1
    Digitale Medien
    Digitale Medien
    Sodium-Calcium Exchange in Vascular Smooth Muscle (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 639 (1991), S. 0 
    Details
    ISSN: 1749-6632
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Allgemeine Naturwissenschaft
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1111/j.1749-6632.1991.tb17343.x
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  • 2
    Digitale Medien
    Digitale Medien
    Hydrogen chloride reaction with lime and limestone: kinetics and sorption capacity (1992)
    s.l. : American Chemical Society
    Industrial & engineering chemistry research 31 (1992), S. 164-171 
    Details
    ISSN: 1520-5045
    Quelle: ACS Legacy Archives
    Thema: Chemie und Pharmazie , Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1021/ie00001a023
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  • 3
    Digitale Medien
    Digitale Medien
    In vivo inhibition of etoposide-mediated apoptosis, toxicity, and antitumor effect by the topoisomerase II-uncoupling anthracycline aclarubicin (1994)
    Springer
    Cancer chemotherapy and pharmacology 34 (1994), S. 503-508 
    Details
    ISSN: 1432-0843
    Schlagwort(e): Key words: Etoposide – Topoisomerase II – Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract. A number of clinically important drugs such as the epipodophyllotoxins etoposide (VP-16) and teniposide (VM-26), the anthracyclines daunorubicin and doxorubicin (Adriamycin), and the aminoacridine amsacrine exert their cytotoxic action by stabilizing the cleavable complex formed between DNA and the nuclear enzyme topoisomerase II. We have previously demonstrated in several in vitro assays that the anthracycline aclarubicin (aclacinomycin A) inhibits cleavable-complex formation and thus antagonizes the action of drugs such as VP-16 and daunorubicin. The present study was performed to validate these in vitro data in an in vivo model. At nontoxic doses of 6 and 9 mg/kg, aclarubicin yielded a marked increase in the survival of non-tumor-bearing mice given high doses of VP-16 (80 – 90 mg/kg) in six separate experiments. In therapy experiments on mice inoculated with Ehrlich ascites tumor cells, aclarubicin given at 6 mg/kg roughly halved the increase in median life span induced by VP-16 at doses ranging from 22 to 33 mg/kg. An attempt to determine a more favorable combination of VP-16 and aclarubicin by increasing VP-16 doses failed, as the two drugs were always less effective than VP-16 alone. The way in which VP-16-induced DNA strand breaks lead to cell death remains unknown. However, VP-16 has been reported to cause apoptosis (programmed cell death) in several cell lines. To ascertain whether the protection given by aclarubicin could have a disruptive effect on the apoptotic process, we used the small intestine as an in vivo model. Whereas VP-16-induced apoptosis in crypt stem cells was detectable at a dose as low as 1.25 mg/kg, aclarubicin given at up to 20 mg/kg did not cause apoptosis. Indeed, aclarubicin caused a statistically significant reduction in the number of cells rendered apoptotic by VP-16. The present study thus confirms the previous in vitro experiments and indicates the value of including an in vivo model in a preclinical evaluation of drug combinations.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00685662
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  • 4
    Digitale Medien
    Digitale Medien
    Spontaneous echo contrast imaging in infective endocarditis: a predictor of complications? (1992)
    Springer
    The international journal of cardiovascular imaging 8 (1992), S. 197-207 
    Details
    ISSN: 1573-0743
    Schlagwort(e): transesophageal echocardiography ; infective endocarditis ; spontaneous echo contrast
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Infective endocarditis is associated with significant morbidity and mortality. Valvular destruction and congestive heart failure are more common in patients with echocardiographically detectable vegetations. In addition, spontaneous platelet aggregation is increased when vegetations are present on cardiac valves. The aim of the study was to assess the prognostic value of spontaneous echo contrast (SEC) imaging, as SEC is supposed to reflect red blood cell aggregates stimulated by platelet activity. We studied 293 patients with clinical signs of infective endocarditis. Vegetations, attached to the aortic or mitral valve, were found in 130 patients (44.4%) who were followed for a mean period of 12 months. In 34 of these 130 patients (26.2%) SEC was imaged during the initial transesophageal echocardiographic examination. In these patients SEC indicated a prolonged healing of infective endocarditis with a specificity of 91.2%, a sensitivity of 77.3%, a positive accuracy of 77.3%, a negative accuracy of 74.3%. Multivariate analysis revealed that SEC is a risk factor for valve replacement (p 〈 0.001) and for embolic events (p 〈 0.001), less for mortality (p 〈 0.01), and lowest for abscess formation (p 〈 0.05). The dose of ADP to induce half-maximal platelet aggregation was significantly lower in patients with SEC (0.71 ± 0.15μl) than without SEC (1.05 ± 0.12μl;p 〈 0.05), implying an increased spontaneous platelet aggregation in the presence of SEC. Our data provide evidence that systemically activated coagulation plays an important role in infective endocarditis. SEC, the echocardiographic implication of an increased platelet aggregation, predicts complications such as thromboembolic events and the need for surgery and is closely related to the prolonged healing period of infective endocarditis. In addition to demonstrating vegetations, transesophageal echocardiography provides information helpful in assigning patients to a high-risk subgroup. Transesophageal echocardiography may play an important role in assessing the clinical outcome of these patients.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01146838
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  • 5
    Digitale Medien
    Digitale Medien
    Control of MAP kinase activation by the mitogen-induced threonine/tyrosine phosphatase PAC1 (1994)
    [s.l.] : Nature Publishing Group
    Nature 367 (1994), S. 651-654 
    Details
    ISSN: 1476-4687
    Quelle: Nature Archives 1869 - 2009
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Notizen: [Auszug] The catalytic domain of PAC1 (amino acids 127-314; cPACl) was expressed as a soluble glutathione S-transferase (GST) fusion protein, and the enzymatic activity of the highly purified GST-cPACl was assayed using a variety of substrates. In a screen of potential physiological substrates, we used ...
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1038/367651a0
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  • 6
    Digitale Medien
    Digitale Medien
    Diagnosis of esophageal motor disorders: A prospective study comparing barium swallow, food barium mixture, and continuous swallows with manometry (1992)
    Springer
    Abdominal imaging 17 (1992), S. 1-4 
    Details
    ISSN: 1432-0509
    Schlagwort(e): Esophagus, motility disorder ; Manometry ; Radiology
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Radiography and manometry of the esophagus were compared in 77 patients consecutively referred for manometric investigation on suspicion of esophageal motility disorder. Radiography and manometry were carried out simultaneously, and the results were assessed blindly. The examination comprised barium swallow, bread barium swallow, and barium swilling. Considering manometry as the standard, the overall sensitivity and specificity of the radiologic examinations were 90.4% and 92.0%, respectively. We conclude that radiology is an excellent investigation for the separation of patients with and without esophageal motility disorders, but correct subclassification often required manometry.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01888495
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  • 7
    Digitale Medien
    Digitale Medien
    Phase II study of high-dose aclarubicin in previously treated patients with small-cell lung cancer (1992)
    Springer
    Cancer chemotherapy and pharmacology 30 (1992), S. 219-220 
    Details
    ISSN: 1432-0843
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00686316
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  • 8
    Digitale Medien
    Digitale Medien
    Comparison of cyclosporin A and SDZ PSC833 as multidrug-resistance modulators in a daunorubicin-resistant Ehrlich ascites tumor (1992)
    Springer
    Cancer chemotherapy and pharmacology 30 (1992), S. 235-237 
    Details
    ISSN: 1432-0843
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Recent studies by Boesch et al. have demonstrated that a nonimmunosuppressive cyclosporin analog, SDZ PSC 833 (an analog of cyclosporin D), is an active multidrug-resistance modifier that is at least 10 times more potent than cyclosporin A. In vitro accumulation and cytotoxicity experiments using daunorubicin (DNR) and vincristine (VCR) under the influence of SDZ PSC 833 and cyclosporin A were performed in wild-type (EHR2) and the corresponding highly DNR-resistant (about 80-fold) Ehrlich ascites tumor cells (EHR2/DNR+). In accumulation experiments, both SDZ PSC 833 and cyclosporin A were found to reverse the multidrug-resistant (MDR) phenotype, but to the same degree at equimolar concentrations. Thus, in EHR2/DNR+ cells, both cyclosporins at 5 μg/ml enhanced DNR and VCR accumulation to sensitive levels, but only a negligible effect on DNR accumulation in the drug-sensitive cells was seen. In the clonogenic assay, the cytotoxicity of the two modulators was equal. The lethal dose for 50% of the cell population (LD50) was approx. 7 μg/ml for both compounds, and no toxicity was observed at concentrations below 2 μg/ml. At nontoxic doses, both cyclosporins effectively increased the cytotoxicity of DNR and VCR in a concentration-dependent manner. The dose-response curves were nearly identical and did not demonstrate differences in modulator potency. These data permit the conclusion that cyclosporin A and SDZ PSC 833 do raise the intracellular accumulation of DNR and VCR to the same levels and that SDZPSC 833 does not potentiate cytotoxicity better than cyclosporin A in EHR2/DNR+ cells. However, since the new compound is nonimmunosuppressive and causes less organ toxicity, clinical studies of its MDR modulating effect seem highly relevant.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00686321
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  • 9
    Digitale Medien
    Digitale Medien
    Antitumor activity of the two epipodophyllotoxin derivatives VP-16 and VM-26 in preclinical systems: a comparison of in vitro and in vivo drug evaluation (1990)
    Springer
    Cancer chemotherapy and pharmacology 27 (1990), S. 194-198 
    Details
    ISSN: 1432-0843
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The epipodophyllotoxines VP-16 and VM-26 are chemically closely related. VM-26 has been found to be considerably more potent than VP-16 in vitro in a number of investigations. Although the drugs have been known for 〉20 years, they have not been compared at clearly defined equitoxic doses on an optimal schedule in vivo and it has not been clarified as to whether a therapeutic difference exists between them. A prolonged schedule is optimal for both drugs; accordingly we determined the toxicity in mice using a 5-day schedule. The dose killing 10% of the mice (LD10) was 9.4 mg/kg daily (95% confidence limits, 7.4–11.8) for VP-16 and 3.4 (2.5–4.5) mg/kg daily for VM-26. In vitro, we found VM-26 to be 6–10 times more potent than VP-16 in a clonogenic assay on murine tumors P388 and L1210 leukemia and Ehrlich ascites. This pattern was also demonstrated in a multidrug-resistant subline of Ehrlich selected for resistance to daunorubicin (Ehrlich/DNR+), as it was 30 times less sensitive than Ehrlich cells to both VP-16 and VM-26. Using 90%, 45%, and 22% of the LD10 on the same murine tumors in vivo, we found that the effect of the two drugs was equal as evaluated by both the increase in life span and the number of cures. The drugs were also compared in nude mice inoculated with human small-cell lung cancer lines OC-TOL and CPH-SCCL-123; however, they were more toxic to the nude mice and only a limited therapeutic effect was observed. In conclusion, the complete cross-resistance between the two drugs suggests that they have an identical antineoplastic spectrum. VM-26 was more potent than VP-16 in vitro; however, this was not correlated to a therapeutic advantage for VM-26 over VP-16 in vivo
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00685712
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  • 10
    Digitale Medien
    Digitale Medien
    Doxorubicin sensitivity pattern in a panel of small-cell lung-cancer cell lines: correlation to etoposide and vincristine sensitivity and inverse correlation to carmustine sensitivity (1992)
    Springer
    Cancer chemotherapy and pharmacology 31 (1992), S. 46-52 
    Details
    ISSN: 1432-0843
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The aim of our investigations is to evaluate whether the sensitivity patterns of small-cell lung-cancer (SCLC) cell lines in vitro can be used in evaluating new drugs and in selecting drugs for the optimization of combination therapy. In our attempts to obtain a panel of cell lines demonstrating differential patterns in sensitivity, we have developed three SCLC lines exhibiting different types of multidrug resistance (MDR). In the present investigations we compared the sensitivity patterns shown by five wild-type SCLC lines and three MDR lines in response to six different types of drugs: doxorubicin, cytarabine, carmustine, cisplatin, vincristine, and etoposide. In the wild-type SCLC cell lines, the range of variation in sensitivity to all drugs was within a factor of 10. Cell lines showing low sensitivity to doxorubicin also exhibited low sensitivity to etoposide and vincristine, and vice versa. In contrast, the pattern of sensitivity to carmustine was almost the opposite of that to doxorubicin. A tendency to an inverse relationship between doxorubicin and carmustine sensitivity was also observed when doxorubicin sensitivity was reduced in near stationary cells and in cells exposed to the metabolic inhibitor 2-deoxy-d-glucose. In agreement with the pattern observed for the wild-type lines, all of the MDR sublines demonstrated collateral sensitivity to carmustine. As to cytarabine, the wild-type lines expressed a sensitivity pattern similar to that shown in response to doxorubicin. Interestingly, the opposite pattern was found in the MDR lines, as all three demonstrated cytarabine hypersensitivity. The combination of alkylating agents and “MDR” drugs are of proven clinical benefit in the treatment of solid tumors, as is the combination of anthracycline and cytarabine in acute myeloid leukemia. The experimentally derived sensitivity data on cytarabine, alkylating agents, and MDR drugs (i.e., etoposide, doxorubicin, vincristine) thus resemble the clinical experience with these drugs, and we conclude that the use of a clonogenic asay on the described panel of SCLC cell lines can give valuable information for the selection of agents for combination therapy.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00695993
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